Original Report: Patient-Oriented, Translational Research American

Journal of

Nephrology

Am J Nephrol 2014;39:491–498 DOI: 10.1159/000362744

Received: October 30, 2013 Accepted: April 3, 2014 Published online: May 21, 2014

Predictors of Sustained Arteriovenous Access Use for Haemodialysis Sokratis Stoumpos Kathryn K. Stevens Emma Aitken David B. Kingsmore Marc J. Clancy Jonathan G. Fox Colin C. Geddes Glasgow Renal and Transplant Unit, Glasgow, UK

Abstract Background: Guidelines encourage early arteriovenous (AV) fistula (AVF) planning for haemodialysis (HD). The aim of this study was to estimate the likelihood of sustained AV access use taking into account age, sex, comorbidity, anatomical site of first AVF and, for pre-dialysis patients, eGFR and proteinuria. Methods: 1,092 patients attending our centre who had AVF as their first AV access procedure between January 1, 2000 and August 23, 2012 were identified from the electronic patient record. The primary end-point was time to first sustained AV access use, defined as use of any AV access for a minimum of 30 consecutive HD sessions. Results: 52.9% (n = 578) of the patients ultimately achieved sustained AV access use. The main reasons for AV access non-use were AVF failure to mature and death. The 3-year Kaplan-Meier probability of sustained AV access use was 68.8% for those not on renal replacement therapy (RRT) (n = 688) and 74.2% for those already on RRT (n = 404) at the time of first AVF. By multivariate analysis in patients not on RRT, male sex (HR 2.22; p < 0.001), uPCR (HR 1.03; p = 0.03) and eGFR (hazard

© 2014 S. Karger AG, Basel 0250–8095/14/0396–0491$39.50/0 E-Mail [email protected] www.karger.com/ajn

ratio, HR 0.85; p < 0.001) were independent predictors of AV access use. In patients already on RRT, age (HR 0.98; p < 0.001) and peripheral vascular disease (HR 0.48; p = 0.02) were independent predictors of AV access use. Conclusion: Our data suggest that refinement of the current guideline for timing of AV access creation in planning RRT is justified to take into account individual factors that contribute to the likelihood of technical success and clinical need. © 2014 S. Karger AG, Basel

Introduction

Selection criteria and optimal timing for vascular access creation in patients with advanced chronic kidney disease (CKD) remain controversial. Arteriovenous (AV) fistula (AVF) remains the vascular access of choice but successful creation must occur in advance of needing dialysis if a central venous cannula (CVC) is to be avoided. The likelihood of success and time to maturation are difficult to predict for individual patients [1, 2]. Current

This study was presented at the Annual Meeting of the Renal Association, Bournemouth, UK, March 13–15, 2013.

Colin C. Geddes Glasgow Renal and Transplant Unit Western Infirmary, Dumbarton Road Glasgow G11 6NT (UK) E-Mail colin.geddes @ ggc.scot.nhs.uk

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Key Words Arteriovenous access · Arteriovenous fistula · Arteriovenous graft · Chronic kidney disease · Haemodialysis

Subjects and Methods The study was a single-centre retrospective observational cohort study from the Glasgow Renal and Transplant Unit; this serves a population of approximately 1.6 million in the West of Scotland, with a prevalent HD population of approximately 600 patients attending 7 HD centres. The decision to refer for AV ac-

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Am J Nephrol 2014;39:491–498 DOI: 10.1159/000362744

cess is made by the nephrologists with the aim of having AV access ready before the need for dialysis where possible in all patients unless the patient refuses, there are psychological or physical reasons why the patient might be at high risk of needle dislodgement, or the patient is predicted to have only a few months to live. Patients are referred to renal access surgeons. The surgeons assess referred patients clinically and, in recent years, surgery has been guided by Doppler ultrasound mapping of vessels. The unit was formed in 2010 by the merging of two similar sized renal units. The same surgical team (consisting 12 vascular access surgeons over the period) carried out AV access procedures. Before 2010, the analysis includes the procedures performed in only one of these units, as the data were not available for the other unit before the merge. All patients who had first AV access procedure between January 1, 2000 and August 23, 2012 were identified from the prospectively maintained electronic patient record. During this period a total of 1,283 patients started HD for established renal failure in the same catchment population. We excluded 14 patients who had synthetic AV graft as their first AV access. For the patients who had more than one AV access created, the date of first AVF creation was used though it might not be the one subsequently first used for HD. We excluded patients who were receiving HD before January 1, 2000 but included those on other renal replacement therapy (RRT) modalities (peritoneal dialysis and transplant) before 2000 who subsequently had a first AV access procedure for HD. We also recorded the dates of second, third and fourth new AV access creations in individual patients. Baseline Data Age, sex, duration of RRT at the time of access creation and the presence of diabetes mellitus (DM), ischaemic heart disease (IHD) and peripheral vascular disease (PVD) at baseline were recorded. In the subgroup of patients not yet on RRT at the time of first AV access creation (CKD stages 4 or 5), the last eGFR (Modification of Diet in Renal Disease (MDRD) 4 formula) [7] and uPCR before AV access creation were calculated. If no uPCR value was available, 24-hour urine protein excretion was used, dividing the value in mg by 10 to achieve an equivalent in mg/mmol [8]. Outcome Assessment AV access use for individual HD sessions was identified from the vascular access recorded in the electronic record by the dialysis nurse for each individual HD session. Sustained AV access use was arbitrarily defined, as there is no definition in the literature. A minimum of 30 consecutive HD sessions was set which corresponds to approximately 3 months of continuous AV access use. Based on clinical experience, we felt that AV access use for a shorter period was not of sufficient benefit to the patient to outweigh the morbidity associated with AV access creation. The primary end-point was time from first AV access creation to sustained AV access use, or any other possible outcome if AV access was not used. In patients who never achieved sustained AV access use, follow-up was censored on date of death, date lost to follow-up or date of last entry in the electronic patient record, whichever was first. We also calculated the failure to mature (FTM) rate for first AVF in our centre and recorded subsequent AV access creations to enable calculation of the number of AVF access creations before sustained AV access use.

Stoumpos/Stevens/Aitken/Kingsmore/ Clancy/Fox/Geddes

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strategies encourage relatively early access planning which inevitably means that some patients undergo creation of AV access that is never used for dialysis. Reasons for ultimate failure to use AV access can include technical aspects of AV access creation (AVF failure to mature) or factors relating to CKD (renal function that does not deteriorate as anticipated, pre-emptive renal transplant or death before reaching established renal failure). Evidence to guide the optimal timing of AV access creation is lacking and clinical practice guidelines for vascular access creation are largely opinion-based and quite variable. For example, the 2011 UK Renal Association guidelines recommend that the exact timing of placement of vascular access should be determined by the rate of decline of renal function, comorbidities and by the surgical pathway [3]. Kidney Disease Outcomes Quality Initiative (KDOQI) recommends that an AVF should be created at least 6 months before the expected start of haemodialysis (HD) [4]. In contrast, both 2007 European Best Practice Guidelines and 2006 Canadian Society of Nephrology guidelines recommend establishment of AVF when patients reach stage 4 CKD or earlier in case of progressive kidney disease or specific clinical conditions such as diabetes or severe peripheral vascular disease [5, 6]. It would be helpful to clinicians to be able to individualize the likelihood of AV access use when deciding when to recommend AV access creation. This depends on factors associated with the technical success of AV access formation and, in the case of patients not yet on dialysis, factors associated with progression of CKD. The aim of this retrospective observational study was to estimate the likelihood of sustained AV access use in patients having their first AV access formation taking into account age, sex, comorbidity, anatomical site of first AVF and, in the case of patients not yet on dialysis, eGFR and proteinuria. Our hypothesis was that older, female patients, patients with diabetes and vascular comorbidity would be less likely to achieve sustained AV access use because of lower AV access technical success, and in patients not yet on dialysis, higher eGFR, lower proteinuria and older age would be associated with lower probability of sustained AV access use because of slower deterioration in renal function.

Results

Table 1. Outcomes after first AV access creation

Patients not on RRT (n = 688)

Patients on RRT (n = 404)

AV access use

355 (51.6)

223 (55.2)

AV access non-use AV access failure to mature Other Death Transplantation or peritoneal dialysis Recovery of renal function Remained pre-dialysis at end of study Lost to follow-up

333 (48.4) 65 (9.4) 253 (36.8) 112 (16.3)

181 (44.8) 110 (27.2) 60 (14.9) 39 (9.7)

14 (2.0) 0

17 (4.2) 4 (1.0)

127 (18.5) 15 (2.2)

0 11 (2.7)

Figures are presented as n (%).

AVF Creation In 238 cases it was not possible to determine retrospectively which artery had been used for first AVF creation. Of the remainder, all 854 were upper limb AVF. 459 (53.7%) were distal utilizing the radial or ulnar artery, and 395 (46.3%) were proximal utilizing the brachial artery. 92 of the 459 patients (20.0%) with distal AVF as their first access subsequently had a second proximal AVF created for vascular access.

Patient Characteristics 1,106 patients had first AV access formed during the study period. 1,092 of these first-access creations were autologous AVF and 14 were synthetic AV grafts. These 14 patients were excluded from further analysis. Average age at the time of first AV access formation was 62.7 years (standard deviation 15.7), 56.5% of the patients were male and median follow-up to study outcome was 0.6 years (interquartile range (IQR) 0.3–1.3). The prevalence of DM, IHD and PVD at the time of first AVF creation was 33.7, 16.1 and 10.0%, respectively. 688 patients who were not yet on RRT (CKD stage 4 or 5) had a median eGFR of 10.7 ml/min/1.73 m2 (IQR 8.6–13.2) and a median uPCR of 206.9 mg/mmol (IQR 93.9–433.1) at the time of first AVF creation. 404 patients were already on RRT with a median duration of RRT of 0.3 years (IQR 0.1–1.2). Patients on RRT before first AV access creation were significantly younger than those who were not on RRT (mean age 60.9 vs. 63.8 years; p = 0.004).

Outcomes after AVF Creation 175 of the 1,092 first AVF failed to mature giving a FTM rate of 16.0%. During the follow-up period, 52.9% (n = 578) of the patients ultimately achieved sustained AV access use: 51.6% (n = 355) of those not on RRT and 55.2% (n = 223) of those on RRT at the time of AVF creation (table 1). 285 patients had a second AV access creation, 56 a third, and 14 a fourth during the study period. In the 578 patients who achieved sustained AV access use, a total of 747 AV access creations were required: 438 (75.8%) achieved sustained use with the first AVF, 116 (20.1%) after a second AV access creation, 19 (3.3%) after a third, and 5 (0.8%) after a fourth. In the patients who were not yet on RRT at the time of first AVF, 333 (48.4%) never achieved sustained AV access use. The main reasons were AV access non-use primarily due to death (n = 112; 16.3%) and AVF FTM (n = 65; 9.4%). Additionally, 127 (18.5%) patients remained pre-RRT by the end of study. Other reasons for AV access non-use in this group were transplantation (n = 13), peri-

Predicting Sustained Arteriovenous Access Use

Am J Nephrol 2014;39:491–498 DOI: 10.1159/000362744

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Statistical Analysis Because the follow-up was variable, we estimated the KaplanMeier probability of sustained AV access use. Actuarial time from date of first AV access creation to sustained AV access use was calculated by Kaplan-Meier survival analysis with univariate comparisons by sex, patient age in five similar sized groups (17–49, 50–60, 61–70, 71–77 and >77 years), first AVF site [distal (radial or ulnar artery) or proximal (brachial artery)] and the presence of DM, IHD and symptomatic PVD at the time of first AVF creation. We analysed separately patients not yet on RRT at the time of first AVF creation, as time to sustained AVF use is dependent on time before RRT becomes necessary in this group of patients. In patients not yet on RRT at the time of first AVF, comparison of pre-defined groups by eGFR (>15, 11–15, 6–10 and 0–5 ml/min/1.73 m2) and uPCR (0–99.9, 100–299.9 and >300 mg/mmol) was also performed. Because of the described changes to the vascular access service over time, we also compared outcomes in two eras: 2000–2008 and 2009–2012. Univariate statistical comparison of actuarial time to sustained AV access use was by log-rank test. We also compared time to sustained AV access use after the second or third AV access creation. Finally, to test the independent association of baseline variables with time to sustained AV access use, two Cox proportional hazards multivariate models were created: in the pre-RRT group (with age, sex, DM, IHD, PVD, distal vs. proximal AVF, eGFR and uPCR as the independent variables), and in the RRT group (with age, sex, DM, IHD, PVD, distal vs. proximal AVF as the independent variables) with time from first AVF creation to sustained AV access use as the dependent variable. The IBM SPSS Statistics Package (version 21.0; SPSS, Inc.) was used for all analyses. In all analyses, a p value